Surface functionalisation using arylcarbene reactive intermediates

ABSTRACT

A process for producing a substrate having a functionalised surface, which process comprises contacting the substrate with a carbene precursor, which carbene precursor is a compound of formula (III) or (IV) whose substituent groups are defined herein: (b) generating a carbene reactive intermediate from the carbene precursor so that it reacts with the substrate to functionalise the surface, thereby yielding an activated substrate; and (c) further functionalising the activated substrate obtained in (b). In (c), the activated substrate may be further functionalised by treating the activated substrate with a diazonium salt for the introduction of colour and/or another desired activity, and/or by treatment with hydrogen peroxide to produce a biocidal substrate. The invention further relates to carbene precursor compounds for use in the surface functionalisation process, and to processes for preparing certain precursor compounds.

This application is the U.S. national phase of International ApplicationNo. PCT/GB2006/000139 filed 17 Jan. 2006 which designated the U.S. andclaims priority to GB 0500895.8 filed 17 Jan. 2005, the entire contentsof each of which are hereby incorporated by reference.

The present invention relates to a process for the surfacefunctionalisation of a substrate using an arylcarbene as the reactiveintermediate. The invention in particular relates to a process for thesurface functionalisation of a polymeric or an inorganic substrate forproducing a substrate which is coloured and/or which has biocidalactivity. The process of the invention can be used to produce biocidalsubstrates in which the biocidal activity is regenerable. The inventionfurther relates to carbene precursor compounds for use in the surfacefunctionalisation process, and to processes for preparing certainprecursor compounds.

Dyestuffs which are used to colour natural and synthetic polymers, viacovalent modification, most commonly rely upon the presence of highlyreactive groups which have been coupled to the chromophoric species.Examples include the Procion and Gibacron range of dyes (which rely uponthe reactivity of a chlorotriazinyl residue with nucleophilic residueson the substrate) and the Remazol range of dyes (which rely on avinylsulfonyl residue as a nucleophilic acceptor for appropriatereactive groups on the polymer). Both of these reactive classes of dyehave preferred substrates, which must possess the required nucleophiliccharacteristics. Development of this type of strategy still continues.However, in addition to the requirement for nucleophilic functionalityon the substrate (usually hydroxyl or amino groups), this approachgenerally requires vigorous conditions, such as high temperature orstrongly basic media, for bond formation to occur.

An alternative technique whereby highly reactive carbene or nitrenespecies are generated from inert precursors under less harsh conditionshas also been investigated for application to dyeing and other surfacemodifying processes of various natural and synthetic polymers. Thechemistry of carbenes and nitrenes is well documented, and thesereactive entities are known to form covalent bonds with many types offunctional group. The application of these species to the surfacemodification of organic solids using different approaches both for thegeneration of the required carbenes or nitrenes, and for their reactionwith the solid surface has been reported.

French Patent No. 1 500 512 describes allowing carbenes to come intocontact with an organic solid. The preferred method for surfacemodification is to allow the volatilised carbene to come into contactwith the polymer. Inherent in this approach, however, are limitations:only volatile (i.e. low molecular weight) carbenes, and those stable torelatively high temperatures, are applicable.

The application of carbenes generated from diazo compounds as suitablereactive dyes has been found to have important limitations, for examplethe ease of generation of the required diazo precursor (D. R. Braybrooket al., J. Photochem. Photobiol A: Chem, 1993, 70, 171) and thestability of the dye to the carbene generating process.

More recently, the use of carbenes carrying pendant activated sidechains for colouration is described in WO 00/26180.

The rapid rise of Methicillin Resistant Staphylococcus Aureus (“GoldenStaph”) and other resistant bacteria has led to a significant increasein persistent bacterial infections in the human population world-wide.This has proved to be a major problem in surgery, particularly wherepost-operative recovery is complicated by infections acquired within thehospital environment. The problem of bacterial infection is notrestricted solely to medical applications, though, and increasingpressure is being brought to bear on industry to control the spread ofbacterial infection. Within the European Union, for instance, theEuropean Biocidal Products Directive (98/9/EC) establishes a duty ofcare by European industries wherever possible to use antibacterialagents to protect the general population against harmful bacteria.

The potential of halogenated furanones and isothiazolones in antifoulingpolymers has been described in WO 99/01514. In this work, an organicantifouling agent was mixed with an extrudable polymer and examined forantifouling properties. However, limitations of this technology are thatit relies on bulk dispersion of an expensive biocidal agent, it isrestricted to a narrow range of polymers, and the polymer cannot be“reprimed”.

These limitations have been addressed to some extent by covalentattachment of the furanone; for instance, the use of plasma activationwith a small sample of polymer types is described in WO 96/01294, wherebiological efficacy is demonstrated.

Alternative strategies have been based on regenerable biocidal polymers.For example, U.S. Pat. No. 5,490,983 relates to immobilised N-halaminesfor disinfectant use. The disinfectant properties of these compounds insolution has been known for many years, for instance in waterpurification and fabrics. The formulations of U.S. Pat. No. 5,490,983involve immobilisation of the biocidal agent in polymeric form, and thebiocidal activity of the polymers is in principle regenerable. However,one intrinsic problem is that the regeneration technique requireschlorine. This is a toxic gas, and strenuous efforts to minimise the useof this compound are being made across all industry. The technique ofU.S. Pat. No. 5,490,983 is therefore of inherently restrictedapplicability.

Limitations to existing technologies for controlling the growth andspread of bacteria and for introducing colour into a polymericsubstrate, including those mentioned above, include the use of toxicreagents and lengthy synthetic procedures, the reliance on bulkdispersion of an expensive biocidal agent, restriction to a narrow rangeof polymers, that the biocidal activity cannot be “reprimed” sinceleakage of the biocidal agent leads to loss of activity, and a limitedapplicability in terms of the range and forms of polymeric substratethat can be functionalised. The present invention aims to address theseissues.

Accordingly, the present invention provides a process for producing asubstrate having a functionalised surface, which process comprises:

(a) contacting the substrate with a carbene precursor, which carbeneprecursor is selected from a compound of the following formula (III):

wherein

A is an aryl or heteroaryl ring;

p is 1, 2, 3, 4 or 5;

R¹ is selected from hydrogen, aryl which is unsubstituted orsubstituted, heteroaryl which is unsubstituted or substituted, C₁-C₁₀alkoxy which is substituted or unsubstituted, C₁-C₁₀ alkylamino which issubstituted or unsubstituted, di(C₁-C₁₀)alkylamino which is substitutedor unsubstituted, C₁-C₁₀ alkylthio which is substituted orunsubstituted, and C₁-C₁₀ alkyl which is unsubstituted or substitutedand which is optionally interrupted by N(R²), O or S wherein R² is H orC₁-C₆ alkyl;

Q is selected from —N(Z₁)(Z₂) and —CH₂—V—(W—R)_(n);

Z₁ and Z₂ are independently selected from aryl which is unsubstituted orsubstituted, heteroaryl which is unsubstituted or substituted, C₁-C₁₀alkoxy which is substituted or unsubstituted, C₁-C₁₀ alkylamino which issubstituted or unsubstituted, di(C₁-C₁₀)alkylamino which is substitutedor unsubstituted, C₁-C₁₀ alkylthio which is substituted orunsubstituted, and C₁-C₁₀ alkyl which is unsubstituted or substitutedand which is optionally interrupted by N(R²), O or S wherein R² is H orC₁-C₆ alkyl;

V is -alk, —O-alk—, -alk-O— or —O-alk—O—, wherein alk is C₁-C₁₀alkylene;

W is a functional group of one of the following formulae (a) to (c):

wherein X is O, S or NH₂ ⁺; and

-   -   R is selected from H, C₁-C₆ alkyl which is unsubstituted or        substituted, aryl which is unsubstituted or substituted and        heteroaryl which is unsubstituted or substituted;    -   and n is 1, 2 or 3;        and a compound of the following formula (IV):

wherein each of A and B, which are the same or different, is an aryl orheteroaryl ring;

-   -   each of Q and Q², which are the same or different, is —N(Z₁)(Z₂)        or —CH₂—V—(W—R)_(n), wherein Z₁, Z₂, V, W, R and n are as        defined above for formula (III); and    -   each of p and r, which are the same or different, is 1, 2, 3, 4        or 5;        (b) generating a carbene reactive intermediate from the carbene        precursor so that it reacts with the substrate to functionalise        the surface, thereby yielding an activated substrate; and        (c) further functionalising the activated substrate obtained in        (b).

In step (c) of the process of the invention as defined above theactivated substrate obtained in step (b) is further functionalised. By“functionalise” as used in this context is meant the introduction of a,or of another, chemical functional group which exhibits desirablephysical or chemical properties, by covalent attachment or by attachmentthrough hydrogen bonding.

The activated substrate may be further functionalised by treating theactivated substrate with a diazonium salt. Additionally oralternatively, the activated substrate may be further functionalised bytreating the activated substrate with hydrogen peroxide, preferablyaqueous hydrogen peroxide.

Typically, for the introduction of colour, step (c) involves treatingthe activated substrate obtained in step (b) with a diazonium salt,thereby forming a diazo coupled coloured substrate. The diazonium saltmay be selected such that the desired colour is obtained, for instancecyan, magenta, yellow, black, red, green, blue or orange. Typically, thediazonium salt is of type ArN₂ ⁺, wherein Ar is substituted orunsubstituted aryl or substituted or unsubstituted heteroaryl, whereinthe aryl or heteroaryl ring may be substituted or unsubstituted at anyor all positions of the Ar group. Typically Ar is substituted orunsubstituted phenyl. Examples include fast black K salt[2,5-dimethoxy-4-((4-nitrophenyl)diazenyl)benzenediazonium chloride] or4-N,N-dimethylaminobenzene diazonium chloride.

Alternatively, the activated substrate obtained in step (b) may betreated with a diazonium salt which is itself functionalised to confer adesired activity on the substrate. Thus, for, the introduction of aparticular desired activity, step (c) may involve treating the activatedsubstrate in step (b) with a functionalised diazonium salt, thefunctionality of which confers the desired activity. The desiredactivity may be a particular hydrophobicity or hydrophilicity, forexample.

For the introduction of biocidal activity, step (c) of the process asdefined above involves treating the activated substrate obtained in step(b) with hydrogen peroxide, to yield a biocidal polymeric substrate.

The activated substrate obtained in step (b) may be treated with both adiazonium salt and hydrogen peroxide. Thus, for the introduction ofcolour and biocidal activity step (c) of the process of the invention asdefined above may comprise: (d) treating the activated substrateobtained in step (b) with a diazonium salt, thereby forming a diazocoupled coloured substrate, and (e) treating the diazo coupled colouredsubstrate obtained in step (d) with hydrogen peroxide.

Alternatively, for the introduction of biocidal activity and a furtherdesired activity, step (c) of the process of the invention as definedabove may comprise: (d′) treating the activated substrate obtained instep (b) with a functionalised diazonium salt, whose functionalityconfers the desired activity, and (e′) treating the diazo coupledsubstrate obtained in (c) with hydrogen peroxide.

Typically, when Q of formula (IV) is —N(Z₁)(Z₂), then Q² is also—N(Z₁)(Z₂), wherein Z₁ is as defined above and may be the same ordifferent for Q and Q², and wherein Z₂ is as defined above and may bethe same or different for Q and Q².

Typically, when Q of formula (IV) is —CH₂—V—(W—R)_(n), then Q² is also—CH₂—V—(W—R)_(n) wherein V, W, R and n are as defined above and may bethe same or different for Q and Q².

Typically, Q of formula (III) is —N(Z₁)(Z₂), and Q and Q² of formula(IV) are both —N(Z₁)(Z₂), wherein Z₁ is as defined above and may be thesame or different for Q and Q², and wherein Z₂ is as defined above andmay be the same or different for Q and Q².

Typically, Z₁ is C₁-C₄ alkyl. Typically, Z₂ is C₁-C₄ alkyl. Z₁ and Z₂may be the same C₁-C₄ alkyl. Typically, p is 1. Typically, r is 1.

In one embodiment, Q of formula (III) and Q and Q² of formula (IV) areboth —CH₂—V—(W—R)_(n) wherein V, W, R and n are as defined above and maybe the same or different for Q and Q². Typically V is —O-alk—, whereinalk is C₁-C₁₀ alkylene. Typically W is a functional group of formula(c). Typically R is substituted or unsubstituted phenyl. Typically n is1.

Typically A is phenyl. Typically B is phenyl.

In one embodiment, the present invention provides a process forproducing a biocidal polymeric substrate, which process comprises:

(a) contacting the substrate with a diaryl carbene precursor, whichprecursor is selected from:

a compound of the following formula (I):

wherein

each of A and B, which are the same or different, is an aryl orheteroaryl ring;

n is an integer of 1 to 3;

y is 0 or an integer of 1 to 5;

z is 0 or an integer of 1 to 5;

provided that y and z are not both 0;

V is -alk, —O-alk—, -alk—O— or -alk—O—, wherein alk is C₁-C₁₀ alkylene;

W is a functional group of one of the following formulae (a) to (c):

wherein X is O, S or NH₂ ⁺; and

-   -   R is selected from H, C₁-C₆ alkyl which is unsubstituted or        substituted, aryl which is unsubstituted or substituted and        heteroaryl which is unsubstituted or substituted; and        a compound of formula (II):

wherein

R is (CH₂)_(m)N(R³)(R⁴),

R³ is C₁-C₄ alkyl,

R⁴ is phenyl,

m is an integer of 1 to 4; and

X is N₂,

(b) generating a carbene reactive intermediate from the diarylcarbeneprecursor so that it reacts with the substrate to functionalise thesurface, thereby yielding an activated substrate; and

(c) treating the activated substrate obtained in step (b) with aqueoushydrogen peroxide to yield a biocidal polymeric substrate. Typically inthis embodiment the diaryl carbene precursor is a compound of formula(I). Typically y is an integer of 1 to 5 and z is an integer of 1 to 5.

The process of the invention offers significant economic and technicalbulk advantages in that only the surface of the polymer is modified, andit is applicable to a diverse range of substrates including but notlimited to natural and synthetic polymers and inorganic solids. Thecolouration of the diazo-coupled coloured substrates does not sufferfrom leaching, and the biocidal activity of the biocidal substrates isregenerable, that is, the polymer can be reactivated multiple times bytreatment with a hydroperoxide solution.

The basic technique for functionalising the surface of a substrate usingdiarylcarbene precursors is described in WO 00/26180. That disclosure isconcerned primarily with the surface functionalisation of a variety ofpolymeric substrates in order to colour the substrate.

The process of the present invention converts otherwise inertsubstrates, such as polymers, into activated substrates which possesssurface functionality that allows the binding of a biocidal agent byaddition of hydrogen peroxide or the addition of a functional group,such as a chromophoric group, by the addition of a diazonium salt. Inthe context of this invention, the biocidal activity is regenerable bysubsequent retreatment of the activated substrate with fresh hydrogenperoxide. The fact that the functionality is confined to the surface ofthe substrate is advantageous because the bulk of the polymer iseffectively sealed in and therefore the bulk properties of the polymer,including mechanical strength, remain unaffected by the biocidal, colouror other properties that are imparted to the surface.

The substrate treated in accordance with the present invention may beany natural or synthetic substrate which is capable of reaction with acarbene reactive intermediate generated from a diarylcarbene precursorof formula (III) or (IV) as defined above. The substrate is typically anatural or synthetic polymer including but not limited to cellulose,polyglycoside, polypeptide polyacrylates, polyacrylics, polyamides,polycarbonates, polyesters, polyethers, polyketones, polyolefins,rubbers, polystyrenics, polysulfones, polyurethanes, polyvinyls andtheir co-polymers; or an inorganic material including but not limited tosilica, alumina, titania, glasses, and allotropes of carbon such asdiamond, diamond-like carbon, graphite, fullerenes and nanotubes.

Where the substrate comprises a polymer, the molecular weight of thepolymeric substrate may be selected according to the particular utilityof the end product. For example, where the polymeric substrate treatedin accordance with the present invention has biocidal properties, themolecular weight of the polymeric substrate may be selected according tothe particular utility of the biocidal end product. In one embodiment,the substrate is selected from homopolymers and copolymers of ethyleneor propylene, polyesters, polyamides, polystyrene,polytetrafluoroethylene, nylon, silica, cotton, silk and wool. In oneembodiment of the invention the polymeric substrate is in a form thathas a high surface area, for instance a powder or beads.

The polymer may be a homopolymer or a copolymer, for instance a blockcopolymer. It may thus be derived from monomeric units which are thesame or different.

The polymer may be modified, for instance by admixture with an inorganicmaterial. The substrate may thus comprise both a polymer and aninorganic material, for instance a mixture of a polymer and an inorganicmaterial such as an inorganic filler. The substrate may, for example,comprise a mixture of one or more of the polymers referred to above andone or more of the inorganic materials referred to above. Modifiedpolymers of this type are suitable for use in, for instance,semiconductor applications. Technical problems can arise when polymersare used as coating or bonding agents with semiconductors, owing totheir different behaviour on heating. The inclusion of an inorganicfiller with a polymer serves to modify the thermal properties of thepolymer and make it better suited for use together with a semiconductor.

The diarylcarbene precursors of formula (I) are novel compounds. Thepresent invention therefore further provides a compound of formula (I):

wherein

each of A and B, which are the same or different, is an aryl orheteroaryl ring;

n is an integer of 1 to 3;

y is 0 or an integer of 1 to 5;

z is 0 or an integer of 1 to 5;

provided that z and y are not both 0;

V is -alk, —O-alk—, -alk—O— or —O-alk—O—, wherein alk is C₁-C₁₀alkylene;

W is a functional group of one of the following formulae (a) to (c):

wherein X is O, S or NH₂ ⁺; and

-   -   R is selected from H, C₁-C₆ alkyl which is unsubstituted or        substituted, aryl which is unsubstituted or substituted, and        heteroaryl which is unsubstituted or substituted; provided that        the compound is not        4,4′-bis(N-acetyl-2-aminoethyl)diphenyldiazomethane.

Typically, z and y are not both 1.

In one embodiment of formula (I), y is an integer of 1 to 5 and z is aninteger of 1 to 5.

A C₁-C₁₀ alkyl group is an unsubstituted or substituted, straight orbranched chain saturated hydrocarbon radical. Typically it is C₁-C₆alkyl, for example methyl, ethyl, propyl, butyl, pentyl or hexyl, orC₁-C₄ alkyl, for example methyl, ethyl, i-propyl, n-propyl, t-butyl,s-butyl or n-butyl. When an alkyl group is substituted it typicallybears one or more substituents selected from C₁-C₆ alkyl which isunsubstituted, aryl, cyano, amino, C₁-C₁₀ alkylamino,di(C₁-C₁₀)alkylamino, amido, hydroxy, halo, carboxy, C₁-C₆ alkoxy,haloalkyl, sulfonic acid, sulfhydryl (i.e. thiol, —SH), C₁-C₁₀ thioetherand sulfonyl. Examples of substituted alkyl groups include haloalkyl,hydroxyalkyl, aminoalkyl and alkoxyalkyl groups.

An aryl group is a substituted or unsubstituted, monocyclic or bicyclicaromatic group which typically contains from 6 to 14 carbon atoms,preferably from 6 to 10 carbon atoms in the ring portion. Examplesinclude phenyl, naphthyl, indenyl and indanyl groups. An aryl group isunsubstituted or substituted. When an aryl group as defined above issubstituted it typically bears one or more substituents selected fromC₁-C₆ alkyl which is unsubstituted, aryl which is unsubstituted, cyano,amino, amido, hydroxy, halo, carboxy, C₁-C₆ alkoxy, haloalkyl, sulfonicacid and sulfonyl. Typically it carries 0, 1, 2 or 3 substituents.

An alkylene group is unsubstituted or substituted, straight or branchedchain saturated divalent hydrocarbon group. Typically it is C₁-C₈alkylene, for instance C₁-C₆ alkylene. Preferably it is C₁-C₄ alkylene,for example methylene, ethylene, i-propylene, n-propylene, t-butylene,s-butylene or n-butylene. It may also be pentylene, hexylene, heptylene,octylene and the various branched chain isomers thereof

A heteroaryl group is typically a 5- to 10 membered mono- or bicyclicheteroaromatic ring. It is generally a 5- or 6-membered ring, containingat least one heteroatom selected from O, S, N, P, Se and Si. It maycontain, for example, 1, 2 or 3 heteroatoms. Examples of heteroarylgroups include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, furanyl,thienyl, pyrazolidinyl, pyrrolyl, oxazolyl, oxadiazolyl, isoxazolyl,thiadiazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, quinolyland isoquinolyl. A heteroaryl group may be unsubstituted or substituted,for instance, as specified above for alkyl. Typically it carries 0, 1, 2or 3 substituents.

As used herein the term amino represents a group of formula —NH₂. Theterm C₁-C₁₀ alkylamino represents a group of formula —NHR′ wherein R′ isa C₁-C₁₀ alkyl group, preferably a C₁-C₆ alkyl group, as definedpreviously. The term di(C₁-C₁₀)alkylamino represents a group of formula—NR′R″ wherein R′ and R′ are the same or different and represent C₁-C₁₀alkyl groups, preferably C₁-C₆ alkyl groups, as defined previously.

A C₁-C₁₀ alkylthio group is a said C₁-C₁₀ alkyl group attached to a thiogroup.

A C₁-C₁₀ alkoxy group is a said C₁-C₁₀ alkyl group attached to an oxygenatom. A C₁-C₆ alkoxy group is a said C₁-C₆ alkyl group attached to anoxygen atom. A C₁-C₄ alkoxy group is a C₁-C₄ alkyl group attached to anoxygen atom. Examples of C₁-C₄ alkoxy groups include, —OMe (methoxy),—OEt (ethoxy), —O(nPr) (n-propoxy), —O(iPr) (isopropoxy), —O(nBu)(n-butoxy), —O(sBu) (sec-butoxy), —O(iBu) (isobutoxy), and —O(tBu)(tert-butoxy).

Alkylene and alkyl groups may be interrupted by one or more heteroatomsor heterogroups, such as S, O or N(R²) wherein R² is H or C₁-C₆ alkyl.The phrase “optionally interrupted” as used herein thus refers to aC₁-C₁₀ alkyl group or an alkylene group, as defined above, which isuninterrupted or which is interrupted between adjacent carbon atoms by aheteroatom such as oxygen or sulfur, or a heterogroup such as N(R²)wherein R² is H or C₁-C₆ alkyl.

For instance, a C₁-C₁₀ alkyl group such as n-butyl may be interrupted bythe heterogroup N(R²) as follows: —CH₂N(R²)CH₂CH₂CH₃,—CH₂CH₂N(R²)CH₂CH₃, or —CH₂CH₂CH₂N(R²)CH₃. Similarly, an alkylene groupsuch as n-butylene may be interrupted by the heterogroup N(R²) asfollows: —CH₂N(R²)CH₂CH₂CH₂—, —CH₂CH₂N(R²)CH₂CH₂—, or—CH₂CH₂CH₂N(R²)CH₂—.

It is believed that hydrogen bonding is involved in the binding of thesubstituents Q and/or Q² to peroxide. The reactivity of the diazocompound and its derived carbene could be modified by including electronreleasing or electron withdrawing groups on the aromatic rings.

In formula (III) the or each group Q may occupy any available positionon ring A. In formula (IV) the or each group Q and the or each group Q²may occupy any available position on rings A and B respectively. Whenparameter “p” is 1, A is mono-substituted at any ring position by Q; forinstance, when A is a phenyl group it may be substituted at any ofpositions 2, 3, 4, 5 and 6. When parameter “p” is 2, A is di-substitutedat any two positions by Q; for instance, when A is a phenyl group it maybe 2,3- 2,4-, 2,5-, 2,6-, 3,4- or 3,5-disubstituted. When parameter “p”is 3, A is tri-substituted at any three positions by Q; for instance,when A is a phenyl group it may be 2,3,4-, 2,4,5- or3,4,5-tri-substituted. Likewise, when parameter “r” is 1, B ismono-substituted at any ring position by Q²; for instance, when B is aphenyl group it may be substituted at any of positions 2, 3, 4, 5 and 6.When parameter “r” is 2, B is di-substituted at any two positions by Q²;for instance, when B is a phenyl group it may be 2,3- 2,4-, 2,5-, 2,6-,3,4- or 3,5-disubstituted. When parameter “r” is 3, B is tri-substitutedat any three positions by Q²; for instance, when B is a phenyl group itmay be 2,3,4-, 2,4,5- or 3,4,5-tri-substituted.

In formula (I) the or each chain —[CH₂—V—(W—R)_(n)] may occupy anyavailable position on rings A and B. When parameter “y” is 1, B ismono-substituted at any ring position by —[CH₂—V—(W—R)_(n)]; forinstance, when B is a phenyl group it may be substituted at any ofpositions 2, 3, 4, 5 and 6. When parameter “y” is 2, B is di-substitutedat any two positions by —[CH₂—V—(W—R)_(n)] for instance, when B is aphenyl group it may be 2,3- 2,4-, 2,5-, 2,6-, 3,4- or 3,5-disubstituted.When parameter “y” is 3, B is tri-substituted at any three positions by−[CH₂—V—(W—R)_(n)]; for instance, when B is a phenyl group it may be2,3,4-, 2,4,5- or 3,4,5-tri-substituted.

Likewise, when parameter “z” is 1, A is mono-substituted at any ringposition by —[CH₂—V—(W—R)_(n)]; for instance, when A is a phenyl groupit may be substituted at any of positions 2, 3, 4, 5 and 6. Whenparameter “z” is 2, A is di-substituted at any two positions by—[CH₂—V—(W—R)_(n)]; for instance, when A is a phenyl group it may be2,3- 2,4-, 2,5-, 2,6-, 3,4- or 3,5-disubstituted. When parameter “z” is3, A is tri-substituted at any three positions by —[CH₂—V—(W—R)_(n)];for instance, when A is a phenyl group it may be 2,3,4-, 2,4,5- or3,4,5-tri-substituted.

Parameter “n” qualifies the moiety represented by −W—R and thus definesthe number of hydrogen-bonding groups W that are present in thecompounds of formulae (I), (Ia), (III) and (IV). When n is 2 or 3, themoiety —V—(W—R)_(n) in the chain —[CH₂—V—(W—R)_(n)] may be represented,for instance, as —(CR′₂)_(p)—CR′(W—R)₂, —O—(CR′₂)_(p)—CR′(W—R)₂,—(CR′₂)_(p)—C(W—R)₃ or —(CR′₂)_(p)—C(W—R)₃ wherein p is 0 or an integerof 1 to 10 and each R′ is, independently, H or C₁-C₆ alkyl.

In one embodiment, the compound of formula (I) or formula (III) is ofthe following formula (Ia):

wherein each of y, V, W and R is as defined above.

In another embodiment, the compound of formula (I) or formula (III) isof the following formula (Ib):

wherein each of V, W and R is as defined above.

A preferred example of a carbene precursor compound of formula (III) or(IV) is 1-{2-[4-(diazo-phenyl-methyl)-benzyloxy]-ethyl}-3-phenyl urea,hereafter compound XIII. This compound may be produced as shown in thefollowing scheme 1. 4-Bromomethylbenzophenone, which can be preparedaccording to D. D. Tanner et al., J. Org. Chem., 1980, 45, 5177, isfirst coupled with ethanolamine. The resulting benzophenone may beconverted to the urea compound by treatment with phenyl isocyanate indry dichloromethane. The urea compound may be converted to the hydrazoneby treatment with hydrazine hydrate in refluxing methanol overnight,followed by removal of the solvent and extraction into dichloromethane.Oxidation of the hydrazone to the corresponding diazo diarylcarbeneprecursor may conveniently be performed using mercuric oxide in ether,or any other suitable oxidant.

Carbene precursor compounds of formulae (III) or (IV) in which Q and/orQ² is CH₂—V—(W—R)_(n), as defined above, may be produced by analogy withthe method shown in scheme 1, from starting materials which arecommercially available or which may readily be synthesised by knowntechniques.

Diarylcarbene precursors of formula (II) are known from WO 00/26180. Apreferred example of a compound of formula (II) is4-([N-ethyl-N-phenyl-2-aminoethyl]oxymethyl)phenyl phenyl diazomethane,hereafter compound XVI. This compound may be produced as shown in thefollowing scheme 2:

A preferred example of a compound of formula (III) or (IV) isbis-4,4′-N,N-dimethylamino diphenyldiazomethane, hereafter compound 3.This compound may be produced as shown in the following Scheme 3.Michler's ketone (1) can be converted to the known hydrazone (2) byreaction with hydrazine hydrate in ethanol. This hydrazone can beoxidised to diazomethane (3) using yellow mercuric oxide intetrahydrofuran.

Carbene precursor compounds of formulae (III) or (IV) in which Q and/orQ² is —N(Z₁)(Z₂), as defined above, may be produced by analogy with themethod shown in scheme 3, from starting materials which are commerciallyavailable or which may readily be synthesised by known techniques.

The method shown in Scheme 3 includes a new procedure for thepreparation of the key intermediate 2. This procedure for preparingcompound 2 represents a substantial simplification and improvement overthe literature protocol (S. Hünig et al., Eur. J. Org. Chem, 2002, 10,1603-1613).

Accordingly, the present invention further provides a process forproducing a compound of formula (VII) or (VIII):

wherein A is an aryl or heteroaryl ring;

B is an aryl or heteroaryl ring;

p is 1, 2, 3, 4 or 5;

r is 1, 2, 3, 4 or 5;

R¹ is selected from hydrogen, aryl which is unsubstituted orsubstituted, heteroaryl which is unsubstituted or substituted, C₁-C₁₀alkoxy which is substituted or unsubstituted, C₁-C₁₀ alkylamino which issubstituted or unsubstituted, di(C₁-C₁₀)alkylamino which is substitutedor unsubstituted, C₁-C₁₀ alkylthio which is substituted orunsubstituted, and C₁-C₁₀ alkyl which is unsubstituted or substitutedand which is optionally interrupted by N(R²), O or S wherein R² is H orC₁-C₆ alkyl;

Q is —N(Z₁)(Z₂);

Q², which may be the same as or different from Q, is —N(Z₁)(Z₂);

Z₁ and Z₂ are independently selected from aryl which is unsubstituted orsubstituted, heteroaryl which is unsubstituted or substituted, C₁-C₁₀alkoxy which is substituted or unsubstituted, C₁-C₁₀ alkylamino which issubstituted or unsubstituted, di(C₁-C₁₀)alkylamino which is substitutedor unsubstituted, C₁-C₁₀ alkylthio which is substituted orunsubstituted, and C₁-C₁₀ alkyl which is unsubstituted or substitutedand which is optionally interrupted by N(R²), O or S wherein R² is H orC₁-C₆ alkyl;

the process comprising treating a compound of formula (V) or (VI) withhydrazine in the presence of heat and a solvent:

wherein A, B, Q, Q², p, r and R¹ are as defined above.

Typically, hydrazine is used in the form of hydrazine hydrate. Anysuitable solvent is employed, for instance a polar protic solvent suchas an alcohol. Typically, the solvent is ethanol. The reaction iscarried out with heating, typically at the reflux temperature of thesolvent used. For example, when the solvent is ethanol the reaction issuitably carried out at a temperature of 78° C. or higher, e.g. at atemperature of 80° C.

The resulting compounds of formulae (VII) and (VIII) may subsequently beconverted into carbene precursor compounds of formulae (III) and (IV),respectively, as defined above. Accordingly, in one embodiment, theprocess as defined above further comprises oxidising a compound offormula (VII) or (VIII) to produce a carbene precursor compound offormula (III) or (IV) respectively:

wherein A, B, Q, Q², p, r and R¹ are as defined above.

Any suitable oxidant may be used. Typically, the oxidant is mercuricoxide in an aprotic polar solvent, for instance tetrahydrofuran (THF) oran ether. More typically, this oxidation is conducted in the presence ofa base, for instance a metal hydroxide and sodium sulphate. The metalhydroxide is typically an alkali metal hydroxide, for instance potassiumhydroxide. A saturated solution of the metal hydroxide is generallyused. The solvent used for the metal hydroxide is suitably a polarprotic solvent such as an alcohol, for instance ethanol. The solventused for the solution of the compound of formula (VII) or (VIII) issuitably a polar aprotic solvent, for instance tetrahydrofuran.

The carbene precursor compound of formula (III) or (IV) thus producedmay be employed as the carbene precursor in step (a) of the process ofthe invention for producing a substrate having a functionalised surface,as defined above.

By “carbene reactive intermediate”, as used herein, is meant a reactivespecies comprising a formally divalent carbon atom. The carbene reactiveintermediate is generated from the carbene precursor of formula (II) or(IV) by treatment under conditions which result in an irreversiblecovalent reaction with the substrate. Generally the carbene is generatedby heating or irradiating the substrate and pre-adsorbed carbeneprecursor compound; since the carbene precursor of formula (II) or (Iv)is usually intensely coloured (red-orange), the formation and insertionof the carbene is most conveniently monitored by decolourisation.

The coloured substrates produced by the process of the present inventionmay be used in the dye industry for the preparation of non-leaching dyedpolymers, such an example would be in food and drink packaging; they maybe used to confer specific wavelength absorbing properties such asultraviolet or infrared absorption; the ability of the substrates toshow photochromism could be utilised in the medical market for contactlenses; the introduction of fluorescent markers allows security taggingapplications. The coloured substrates produced by the present inventionare capable of being irreversibly dyed with little or no leaching fromthe surface, which is an important practical advantage associated withtheir use.

The biocidal polymeric substrates produced by the process of the presentinvention may be used in many different fields, but they particularlyhave utility in any context where the occurrence of bacterial, viral orfungal infection is a risk. For instance, they may have medical,industrial, catering, domestic, public health or military applications.Hydrogen peroxide-based biocidal agents are tasteless and odourless andare therefore preferable in many contexts to chlorine-based biocides.

The biocidal polymeric substrates are effective against a wide range ofmicro-organisms including Gram-positive and Gram-negative bacteria, aswell as viruses. Specific examples of bacteria include S. Aureus and E.Coli.

Specific examples of the downstream uses of biocidal polymericsubstrates produced by the process of the present invention include usein water purification systems, both small-scale and industrial; use inwater filtration systems, for instance water filter cartridges fordomestic and military use, in emergency applications and disasterrelief; use in air purification systems, for instance air recirculationsystems in aircraft, breathing apparatus and environmental protectionproducts; use in medical and military equipment and clothing such assurgical gowns, surgical masks and surgical instruments; and use inmedical devices such as implants, stents and catheters.

The biocidal polymeric substrates produced by the process of the presentinvention are capable of being regenerated on multiple occasions afteruse by treatment with hydrogen peroxide, which is an important practicaladvantage associated with their use. Regeration may be achieved bysimple re-washing of the substrate with aqueous hydrogen peroxide.

The process is extendable from chromophoric and biocidal applications toinclude other chemical and reactive functionality. The process may beused to produce a substrate having a surface of a particularhydrophobicity or hydrophilicity, for example.

The present invention is further illustrated in the Examples whichfollow:

EXAMPLE 1 Preparation of1-{2-[4-(Diazo-phenyl-methyl)-benzyloxy]-ethyl}-3-phenyl Urea (XIII)

4-(Aminoethoxymethyl)benzophenone hydrochloride (X)

To a solution of dry ethanolamine (1.0 g, 16.4 mmol) in dry THF (5 ml)was added sodium hydride (0.7 g, 60% dispersion in mineral oil, 16.4mmol) in several portions over a period of 5 minutes. A further aliquotof dry THF (5 ml) was added and the resulting mixture stirred for 1 h.To this mixture was added a solution of 4-bromomethyl benzophenone (IX)(4.5 g, 16.4 mmol) in dry THF (25 ml). The resulting mixture was allowedto stir for 18 h. before being concentrated in vacuo. The residue waspartitioned between chloroform and water and the organic layercollected, washed with water then extracted with 2M HCl. The combinedacidic extractions were washed once with chloroform before beingconcentrated in vacuo. The residue was dissolved in a 9:1chloroform:methanol mixture and dried over sodium sulfate before beingconcentrated in vacuo to yield (X) (2.6 g, 55%) as a pale yellow solidwhich was used without further purification.

1-[4-Benzoyl-benzyloxyethyl]-3-phenyl urea (XI)

To a stirred suspension of (X) (3.49 g, 12 mmol) in dry DCM (10 ml) wasadded dry triethylamine (10 ml). After 0.25 h. stirring a solution ofphenyl isocyanate (2.14 g, 18 mmol) in dry DCM (10 ml) was added in oneportion. The mixture was stirred for a further 16 h. then quenched withwater (10 ml). The organic layer was collected and washed sequentiallywith water, 2M HCl, and water. The organic layer was dried over MgSO₄and purified by flash chromatography on silica gel eluting with 2:1petrol 40/60:ethyl acetate (R_(f)=0.1) to yield (XI) (3.01 g, 67%) as awhite solid; m.p. 129-132° C.; δH (DMSO-d, 200 MHz) 3.39 (q, 2H, J=5.1Hz, NHCH₂), 3.58 (t, 2H, J=5.0 Hz, OCH₂CH₂), 4.65 (s, 2H, OCH₂Ar), 6.32(t, 1H, J=5.2 Hz CH₂NHC(O)NHAr), 6.90 (t, 1H, J=7.3 Hz, 4″-H), 7.24 (t,2H, J=7.4 Hz, 3″-, 5″-H), 7.44 (d, 2H, J=7.6 Hz, 2″-, 6″-H), 7.56 (m,4H, 3-, 5-, 3′-, 5′-H), 7.70 (m, 5H, 2-, 4-, 6-, 2″-, 6″-H) 8.63 (s, 1H,CH₂NHC(O)NHAr) ppm; δC (DMSO-d, 400 MHz) 39.9 (CH₂CH₂NH), 70.4(CH₂CH₂O), 72.1 (ArCH₂O), 118.4 (2″-, 6″-C), 121.9 (4″-C), 128.1 (2-,6-, 2′-, 6′-C), 129.4 (3″-, 5″-C), 130.4, 130.6 (3-, 5-, 3′-, 5′-C),133.5 (4′-C), 136.9, 138.0 (1-, 1″-C), 141.3 (4-C), 144.4 (1″-C), 156.1(N(H)C(O)NH), 196.3 (Ar₂C(O)) ppm; max 3431 (N—H_(str)), 1724((R(H)N)₂C═O_(str)), 1658 (Ar₂C═O_(str)) cm⁻¹; m/z 375 [M+H]⁺ (5%), 397[M+Na]⁺ (10%), 433 [M+MeCN+NH₄]⁺ (100%); found 375.1703, C₂₃H₂₃N₂O₃requires 375.1709.

1-{2-[4-(Hydrazono-phenyl-methyl)-benzyloxy]-ethyl}-3-phenyl urea (XII)

A solution of (XI) (0.7 g, 1.9 mmol) in methanol (10 ml) was treatedwith hydrazine hydrate (1.9 g, 38 mmol). The resulting solution washeated to a gentle reflux for 16 h., cooled and concentrated in vacuo.The residue was partitioned between DCM and water and the organic layerwas collected, washed with water and dried over MgSO₄. Concentration invacuo yielded (XII) (0.7 g, 99%) as a thick cloudy white oil; δH (CDCl₃,200 MHz) 3.47 (m, 2H, N(H)CH₂CH₂), 3.61 (m, 2H, OCH₂CH₂), 4.43, 4.52 (s,2H, ArCH₂O), 5.49 (s, 2H, NNH₂), 6.55 (m, 1H, CH₂NHC(O)), 6.99 (m, 1H,4″-H), 7.22 (m, 7H, 3-, 3′-, 3″-, 4′-, 5-, 5′-, 5″-H), 7.46 (m, 6H, 2-,2′-, 2″-, 6-, 6′-, 6″-H), 7.80 (m, 1H, ArNHC(O)) ppm; υmax 3435(N—H_(str)), 1734 ((R(H)N)₂C═O_(str)) cm⁻¹; m/z 389 [M+H]⁺ (15%), 447[M+MeCN+NH₄]⁺ (100%); found 389.1973, C₂₃H₂₅N₄O₂ requires 389.1978.

1-{2-[4-(Diazo-phenyl-methyl)-benzyloxy]-ethyl}-3-phenyl urea (XIII)

To a vigorously stirred mixture of yellow mercury oxide (0.18 g, 0.8mmol), sodium sulfate (0.14 g, 1 mmol) and sat. KOH in ethanol (1 ml)was added a solution of (XII) (0.27 g, 0.7 mmol) in THF (10 ml). Themixture was stirred for 16 h. in the dark, then filtered through a padof celite. The filtrate was collected and concentrated in vacuo to yield(XIII) (0.27 g, 100%) as a dark red solid; m.p. 111-115° C., decolurisesat 136° C.; δ H (CDCl₃, 200 MHz) 3.43 (m, 2H, CH₂CH₂NH), 3.69 (m, 2H,CH₂CH₂O), 4.49 (s, 2H, ArCH₂O), 5.80 (bs, 1H, CH₂NHC(O)), 7.02 (m, 1H,4″-H), 7.41-7.44 (m, 13H, Ar—H), 7.44 (s, 1H, ArNHC(O)) ppm; δC (CDCl₃,400 MHz) 40.3 (CH₂NH), 62.4 (CH₂CH₂O), 68.0 (ArCH₂O), 120.3 (4″-C),123.2 (4′-C), 125.0, 125.8, 126.5, 126.7 (2-, 2′-, 2″-, 6-, 6′-, 6″-C),128.9, 129.1, 129.2, 129.3 (1-, 1′-, 3-, 3′-, 3″-, 5-, 5′-, 5″-C),135.0, 138.9 (4-, 1″-C), 156.5 (NHC(O)NH) ppm; υmax 3344 (N—H_(str)),2042 (R₂C═N═N), 1658 ((R(H)N)₂C═O_(str)) cm⁻¹; m/z 445 [M+MeCN+NH₄]⁺(100%).

REFERENCE EXAMPLE 1 Preparation of4-([N-Ethyl-N-phenyl-2-aminoethyl]oxymethyl)phenyl phenyl diazomethane(XVI) 4-([N-Ethyl-N-phenyl-2-aminoethyl]oxymethyl) benzophenone (XIV)

2-(N-Ethylanilino)ethanol (3.03 g, 18.4 mmol, 1.2 eq) in THF (20 cm³)was treated with NaH (60% dispersion in oil, 524 mg, 13.1 mmol, 1.4 eq)and stirred at 20° C. for 1 hour. 4-Bromomethylbenzophenone (IX) (4.21g, 15.3 mmol) was then added and stirring continued for 72 hours. Excesssolvent was removed in vacuo and the residue diluted with DCM, washedwith water and NaHCO₃ solution (sat.), dried (MgSO₄) and solvent removedunder vacuum. The resulting oil was purified by flash chromatography,eluting with petroleum (bp 40-60° C.):EtOAc (9:1), to give the desiredproduct (XIV) as a yellow oil (4.36 g, 80%), R_(f)=0.54 (4:1,petrol:EtOAc) (Found: C, 78.34; H, 6.86; N, 5.29. C₂₄H₂₅NO₂ requires C,80.19; H, 7.01; N, 3.90%); υ_(max) (film/cm⁻¹ 1658 (s), 1598 (s), 1506(s); δ_(H) (200 MHz; CDCl₃) 1.22 (3H, t, J7, CH ₃), 3.49 (2H, q, J7, CH₂CH₃), 3.58-3.79 (4 H, m, OCH ₂CH ₂N), 4.66 (2H, s, ArCH₂O), 6.69-6.79(3H, m, ArH o- and p- to NR₂), 7.28 (2H, dd, J7, 7, ArH m- to NR₂),7.46-7.68 (5H, m, ArH), 7.80-7.88 (4H, m, ArH o- to C═O); δ_(C) (50.3MHz; CDCl₃) 12.2 (CH₃), 45.5 (NCH₂CH₃), 50.1 (NCH₂CH₂O), 68.5 (NCH₂CH₂O), 72.2 (ArCH₂O), 111.8 (ArCH o- to NR₂), 115.8 (ArCH p- to NR₂),127.0, 128.3, 129.3, 130.0 and 130.3 (ArCH o- and m- to C═O and ArCH m-to NR₂), 132.4 (ArCH p- to C═O), 136.8 and 137.7 (40 ArCC═O), 143.2 (40ArCCH₂O), 147.7 (40 ArCNR₂), 196.4 (C═O); n/z (APCI⁺) 360 ([M+H]⁺, 30%);HRMS C₂₄H₂₆O₂N requires 360.1963; found 360.1963.

4-([N-Ethyl-N-phenyl-2-aminoethyl]oxymethyl) benzophenone hydrazone (XV)

The above benzophenone (701 mg, 1.95 mmol) was reacted with hydrazinehydrate yielding the hydrazone (XV) as a colourless oil (710 mg, 97%),υ_(max) (film)/cm⁻¹ 1598 (s), 1506 (s); δ_(H) (500 MHz; CDCl₃) 1.27 and1.31 (3H, 2* t, J7, CH ₃), 3.52 and 3.57 (2H, 2* q, J7, CH ₂CH₃),3.60-3.87 (4H, m, NCH ₂CH ₂O), 4.63 and 4.71 (2H, 2* s, ArCH ₂O), 5.57(2H, br s, NNH ₂), 6.76-6.87 (3H, m, ArH o- and p- to NR₂), 7.30-7.42(7H, m, ArH), 7.53-7.64 (4H, m, ArH o- to C═N); δ_(C) (125.8 MHz; CDCl₃)12.0 (CH₃), 45.1 and 45.2 (NCH₂CH₃), 49.8 (NCH₂CH₂O), 67.8 and 68.1(OCH₂CH₂N), 72.6 and 72.7 (ArCH₂O), 111.5 and 111.6 (ArCH o- to NR₂),115.5 and 115.6 (ArCH p- to NR₂), 126.2, 127.1, 127.7, 127.8, 128.1,128.5, 128.6, 128.9, 129.0 and 129.1 (ArCH), 131.9 and 132.8 (4°ArCCH₂O), 137.7, 137.8, 138.3 and 138.9 (4° ArCC═N), 147.5 (4° ArCNR₂),148.1 (C═NNH₂); m/z (APCI⁺) 374 ([M+H]⁺, 5%), 357 (5%), 209 (100%).

4-([N-Ethyl-N-phenyl-2-aminoethyl]oxymethyl)phenyl phenyl diazomethane(XVI)

The above benzophenone hydrazone (701 mg, 1.88 mmol) was reacted withmercuric oxide and sodium sulphate yielding the diazomethane (XVI) as apurple liquid (690 mg, 99%) (Found: C, 78.06; H, 6.89; N, 12.36.C₂₄H₂₅N₃O requires C, 77.60; H, 6.78; N, 11.31%); υ_(max) (film)/cm⁻¹2037 (s), 1559 (m); δ_(H) (500 MHz; CDCl₃) 1.26-1.32 (3H, m, CH ₃),3.50-3.80 (6H, m, NCH ₂CH₃ and NCH ₂CH ₂O), 4.65 (2H, s, ArCH ₂O),6.78-6.86 (3 H, m ArH o- and p- to NR₂), 7.28-7.65 (11H, m ArH; δ_(C)(125.8 MHz; CDCl₃) 12.1 (CH₃), 45.3 (NCH₂CH₃), 50.0 (NCH₂CH₂O), 67.9(OCH₂CH₂N), 72.8 (ArCH₂O), 111.7 (ArCH o- to NR₂), 115.6 (ArCH p- toNR₂), 125.0, 125.5, 126.3, 128.3, 128.4, 128.7, 129.0, 129.1 and 129.2(4° ArC and ArCH), 135.7 (4° ArCCH₂O), 147.7 (4° ArCNR₂); m/z (APCI⁺)344 ([M−N₂]⁺, 20%), 209 (100).

EXAMPLE 2 Preparation of Functionalised Polymer Beads/Powder

To a solution in dry THF of compound (XIII) described in Example 1, orcompound (XVI) described in Reference Example 1, was added the requiredpolymer and the mixture concentrated in vacuo. The resulting dark redstained polymer was collected and heated using a heat gun until the darkred coloration had disappeared. The resulting solid was placed in theextraction thimble and Soxhlet extracted with acetone for 12 h. Thesolid was collected and dried to yield the functionalised polymer.

TABLE 1 Functionalised polymers prepared Sample Compound PolymerRatio^(a) A XIII Silica 1:1 B XIII XAD-4^(b) 1:1 C XIII UHMWPE^(c) 1:1 DXIII UHMWPE^(c) 2:1 E XIII PTFE^(d) 1:1 F XVI XAD-4^(b) 1:1^(a)Weight-weight Ratio of compound 1 or 2 to polymer used duringfunctionalisation step; ^(b)Amberlite XAD-4 non ionic absorbant (Aldrich21,648-8); ^(c)Ultra high molecular weight polyethylene powder (Aldrich43,426-4 ^(d)Polytetrafluoroethylene beads (Aldrich 18,247-8)^(c)(Sorbsil ™ C₆₀H(40-60 μM) silica gel).

EXAMPLE 3 Hydrogen Peroxide Loading on Functionalised Polymers

Method for Hydrogen Peroxide Loading

A sample of the required polymer was suspended in 50% aqueous hydrogenperoxide for 1 hour and the polymer was collected by filtration andwashed with 1-1.51 of water, collected and treated with a solution of10% potassium iodide in aqueous acetic acid. After standing for 5minutes, a 1% aqueous starch solution was added, and the suspension leftto stand for 1 hr. The resulting dark blue colour solution was titratedwith sodium thiosulfate until the colourless endpoint. The mixture wasleft for a further hour and any further blue coloration of the solutionwas further titrated with sodium thiosulfate.

TABLE 2 Hydrogen peroxide loading on functionalised polymers. Averageloading of Starch- Hydrogen Iodide Loading of hydrogen peroxide Sampletest peroxide/mol g⁻¹ Mol g⁻¹ A + 7.45 × 10⁻⁵ — B + 8.60 × 10⁻⁵; 9.91 ×10⁻⁵ 8.30 × 10⁻⁵ 6.64 × 10⁻⁵ C + 2.50 × 10⁻⁵ 2.50 × 10⁻⁵ D + 6.18 × 10⁻⁵6.18 × 10⁻⁵ E + 1.07 × 10⁻⁵ 1.07 × 10⁻⁵ F +  1.04 × 10⁻⁵; 2.11 × 10⁻⁵;1.27 × 10⁻⁵ 9.82 × 10⁻⁵; 9.41 × 10⁻⁵ XAD-4 (control) − N/D — UHMWPE(control) − N/D — PTFE (control) − N/D — N/D = Not detected; + = bluecolour

EXAMPLE 4 Stability of Hydrogen Peroxide Functionalised Polymer

Method for the stability testing of hydrogen peroxide functionalisedpolymer A sample of the functionalised polymer B (50 mg), described inExample 3, was suspended in 50% aqueous hydrogen peroxide for 18 hr. Thepolymer was collected by filtration and washed with 1-1.51 of water,collected in a stoppered vial and stored at room temperature in adarkened cupboard. At regular time intervals 10 mg samples werecollected and tested for the hydrogen peroxide loading using the aboveprocedure.

TABLE 3 Stability of hydrogen peroxide functionalised polymer B. Loadingof hydrogen Time interval/h peroxide/mol g⁻¹ 0 8.42 × 10⁻⁵ 24 8.01 ×10⁻⁵ 48 9.61 × 10⁻⁵ 72 6.44 × 10⁻⁵ 96 4.13 × 10⁻⁵

EXAMPLE 5 Regenerability of Hydrogen Peroxide Loading on FunctionalisedPolymers

Method for the Regenerability Testing of Hydrogen PeroxideFunctionalised Polymer

A sample of the required polymer (0.05 g) was suspended in 50% aqueoushydrogen peroxide (2 ml) for 18 h. The polymer was collected byfiltration and washed with 1-1.51 of water, collected and treated withsolution of 10% potassium iodide in acetic acid and water. Afterstanding for 5 minutes a 1% aqueous starch solution was added and thesuspension left to stand for 1 h. A positive test for hydrogen peroxidewas the formation of a dark blue coloured solution. This mixture wasthen quenched with sodium thiosulfate until colourless and the polymerfiltered and washed with 1-1.51 of water. The polymer was thenre-suspended in fresh 50% aqueous hydrogen peroxide (2 ml) and the cyclerepeated.

The above procedure was carried out using polymer samples B and Fdescribed in Example 3. The results are shown in the following Table 4:

TABLE 4 Regenerability of hydrogen peroxide functionalised polymers Band F Polymer B Polymer F Cycle Starch iodide test Cycle Starch iodidetest 1 + 1 + 2 + 2 + 3 + 3 + 4 + 4 + 5 + 5 + 6 + 6 + 7 + 7 + + = bluecolour.

EXAMPLE 6 Bioassay

Method for Bioassay

An agar plate inoculated with the chosen organism was punched with 10 mmwells. To these wells was added 20 μl of molten agar. When set thepolymer sample was added to the well so that a thin layer of polymer wasproduced. The well was then sealed with a further 50 μl of molten agar,the plate incubated overnight at 37° C. and the diameter of theinhibition zones measured.

The results obtained with two different microorganism strains are setout in the following Tables 5 and 6.

(a) S Aureus

TABLE 5 Zones of inhibition results against S. Aureus using 10 mm wellsin Hole-Plate Bioassay (against Ceph C standard) Weight of Samplepolymer/mg Zone/mm B (control) 50 N/D B + H₂O₂ 50 25 B + H₂O₂ 50 18 B +H₂O₂ 25 19 F (control) 50 N/D F + H₂O₂ 50 14 F + H₂O₂ 50 12 F + H₂O₂ 5012 XAD-4 + H₂O₂ (control) 50 N/D C (control) 50 N/D C + H₂O₂ 54 N/DUHMWPE + H₂O₂ 51 N/D E (control) 50 N/D E + H₂O₂ 50 N/D PTFE + H₂O₂ 51N/D N/D = Not detected

TABLE 6 Zone of inhibition results against E. Coli using 10 mm wells inHole- Plate Bioassay (against Ceph C standard) Weight of Samplepolymer/mg Zone/mm B (control) 50 N/D B + H₂O₂ 54 17 F (control) 10 N/DF + H₂O₂ 12 12 XAD-4 + H₂O₂ 50 N/D N/D = Not detected.

EXAMPLE 7 Preparation of bis-4,4′-N,N-dimethylamino Diphenyldiazomethane(3)

Bis-4,4′-N,N-dimethylamino diphenyldiazomethane (3) was prepared andpolymers were functionalised as shown in Scheme 4.

4,4-Bis-N,N-dimethylamino benzophenone hydrazone (2)

A suspension of Michler's ketone (5.0 g, 19 mmol) in ethanol (10 ml) wastreated with hydrazine hydrate (5.0 ml, 100 mmol). The resulting mixturewas heated to a gentle reflux for 72 h., cooled and concentrated invacuo. The residue was diluted with 2-propanol (50 ml) and the resultingsolid collected by filtration and dried in vacuo to yield 2 (4.8 g, 91%)as a beige solid; m.p. 151-152° C.; δ_(H) (d₆-DMSO, 200 MHz) 2.89 (s,2H, 2xNCH₃), 2.97 (s, 2H, 2xNCH₃), 5.81 (br s, 2H, NNH₂), 6.64 (d, 2H,J=8.9 Hz, 3-, 5-H), 6.86 (d, 2H, J=8.8 Hz, 3′-, 5′-H), 7.05 (d, 2H,J=8.8 Hz, 2′-, 6′-H), 7.22 (d, 2H, J=8.9 Hz, 2-, 6-H) ppm; δ_(C)(d₆-DMSO, 200 MHz) 40.9 (4x NCH₃), 112.6 (3-, 5-C), 113.2 (3′-, 5′-C),121.1 (1-C), 127.8 (2-, 6-C), 128.7 (1′-C), 130.3 (2′-, 6′-C), 150.6(Ar₂C═NNH₂) ppm; υ_(max) 1626, 1545, 1350, 1180 cm⁻¹; ms 283 ([M+H]⁺,100%), 305 ([M+Na]⁺, 10%).

Bis-4,4′-N,N-Dimethylaniline Diazomethane (3)

To a vigorously stirred mixture of yellow mercury oxide (0.46 g, 2.1mmol), sodium sulfate (0.35 g, 2.5 mmol) and sat. potassium hydroxide inethanol (3 ml) was added a solution of 2 (0.5 g, 1.8 mmol) intetrahydrofuran (10 ml). The mixture was stirred for 18 h. in the dark,then filtered through a pad of celite. The filtrate was collected andconcentrated in vacuo to yield 3 (0.5 g, 100%) as a dark green solid;m.p. 94° C. (dec.); δ_(H) (CDCl₃, 200 MHz) 2.96 (s, 12H, 4xNCH₃), 6.81(d, 4H, J=6.8 Hz, 3-, 3′-, 5-, 5′-H), 7.17 (d, 4H, J=6.8 Hz, 2-, 2′-,6-, 6′-H) ppm; δ_(C) (CDCl₃, 200 MHz) 149.1 (4-, 4′-C), 132.7 (1-,1′-C), 126.8 (3-, 3′-, 5-, 5′-C), 114.0 (2-, 2′-, 6-, 6′-C), 41.1(4xNCH3) ppm; υ_(max) 2020 (Ar₂C═N⁺═N⁻), 1606, 1519, 1356 cm⁻¹.

EXAMPLE 8 Functionalisation of Polymer Beads/Powder/Fabric (4a-q)

To a solution of 3 in either toluene or tetrahydrofuran (10 ml)(Table 1) was added the required polymer and the mixture concentrated invacuo. The polymer was collected and heated in vacuo to 110° C. for 15minutes. The resulting solid was Soxhlet extracted with acetone for 6 hand the solid collected and dried to yield the functionalised polymer4a-q (Table 7).

TABLE 7 Functionalised polymers prepared. Sample Polymer Form Ratio^(a)Solvent^(b) 4a XAD-4^(c) Beads 1:1 Tetrahydrofuran 4b PSXL-S^(d) Sheet1:1 Tetrahydrofuran 4c UHMWPE^(e) Powder 1:1 Tetrahydrofuran 4dSMUHMWPE^(f) Powder 1:1 Tetrahydrofuran 4e PE-S^(g) Film 1:2 Toluene 4fPP^(h) Pellets 1:1 Toluene 4g PP-S^(h) Sheet 1:2 Tetrahydrofuran 4hN-610^(i) Granules 1:4 Tetrahydrofuran 4i Hybond-N Sheet 1:1Tetrahydrofuran 4j Kevlar Fabric 1:1 Tetrahydrofuran 4k Tencel Fabric1:2 Tetrahydrofuran 4l Viscose Fabric 1:2 Tetrahydrofuran 4mNK-Cotton^(j) Fabric 1:2 Tetrahydrofuran 4n MW-Cotton^(k) Fabric 1:2Tetrahydrofuran 4o Cotton wool Fibre 1:1 Tetrahydrofuran 4p PET^(l)Granules 1:4 THF 4q Silica Gel Powder 1:1 THF 4r Alumina Powder 1:1 THF4s Nomex Fabric 1:1 Toluene Table 7 ^(a)Ratio of diazomethane to polymerused during functionalisation step. ^(b)Solvent used for diazoabsorption onto the polymer. ^(c)Amberlite XAD-4. ^(d)Cross LinkedPolystyrene. ^(e)Ultra High Molecular Weight Polyethylene. ^(f)SurfaceModified Ultra High Molecular Weight Polyethylene. ^(g)Polyethylene.^(h)Polypropylene. ^(i)Nylon-610. ^(j)Normal Knitted Cotton.^(k)Mercerised Woven Cotton. ^(l)Poly(ethylene terephthalate).

EXAMPLE 9 Dyeing of Polymers

(i) Fast Black Dyed Polymers 6a-6r

Polymers 4a-r were dyed by immersing the functionalised polymer in a 0.1M solution of fast black K salt 5 in acetone for 18 h. The polymer wasthen collected by filtration and washed with acetone to furnish thecorresponding diazo polymers 6a-r (Table 2, Scheme 5).

(ii) 4-N,N-Dimethylamino Benzene Diazonium Dyed Polymer Preparation of4-N,N-Dimethylamino benzene diazonium chloride (7)

To an ice cold solution of N,N-Dimethyl-p-phenylene diamine (1.0 g, 7.3mmol) in ethanol (10 ml) was added concentrated hydrochloric acid (0.72ml, 7.3 mmol) and isoamyl nitrite (1.6 ml, 12 mmol). The mixture wasstirred for 10 minutes, than diluted with diethyl ether (50 ml). Theresulting solid was filtered and washed with diethyl ether. Drying invacuo yielded 6 (1.1 g, 77%) as a dark green solid. δ_(H) (d₆-DMSO, 200MHz) 3.29 (s, 6H, 2xNCH₃), 7.10 (d, 2H, J=7.8 Hz, 3-, 5-H), 8.30 (d, 2H,J=7.8 Hz, 2-, 6-H) ppm; δ_(C) (d₆-DMSO, 200 MHz) 157.0 (4-C), 134.9 (2-,6-C), 114.8 (3-, 5-C), 89.91 (1-C), 41.4 (2xNCH₃) ppm.

4-N,N-Dimethylamino benzene Diazonium Dyed UHMWPE (8)

UHMWPE 4c was immersed in a 1M solution of 7 in methanol for 18 h. Thepolymer was collected by filtration and washed with acetone, water andmethanol to furnish the corresponding diazo polymer 8 (Table 8).

TABLE 8 Dyed polymers prepared Sample Colour Sample Colour 4a Yellow 4kPale Yellow 6a Black 6k Green/Brown XAD-4 + 5 Brown/Orange Tencel + 5Light Brown 4b Yellow 4l Pale Yellow 6b Black 6l Brown PSXL-S + 5 PaleOrange Viscose + 5 Pale Beige 4c Yellow 4m Pale Yellow 6c Dark Brown 6mDark Brown UHMWPE + 5 White NK-Cotton + 5 Light Brown 4d Yellow 4n PaleYellow 6d Bark brown 6n Dark Brown SMUHMWPE + 5 Pale Pink MW-Cotton + 5Light Brown 4e Pale Yellow 4o White 6e Orange/Brown 6o Dark Brown PE-S +5 Clear Cotton wool + 5 Light Brown 4f Yellow 4p White 6f Black 4p BrownPP + 5 White PET + 5 Light Orange 4g Pale Yellow 4q Light brown 6g DarkOrange 6q Dark Brown PP-S + 5 Clear Silica + 5 White 4h Pale Yellow 4rPale Yellow 6h Brown 6r Black N-610 + 5 Clear Alumina + 5 Orange 4i PaleYellow 4c Yellow 6i Purple 8 Dark green Hybond-N + 5 White UHMWPE + 7White 4j Yellow 6j Black Kevlar + 5 Beige

EXAMPLE 10 Binding of Hydrogen Peroxide to Functionalised Polymers(9a-s, 10)

To a flask containing hydrogen peroxide (50% aqueous solution, 10 ml)was added the functionalised polymer (4a-f or 8) and the mixture allowedto stand at room temperature in the dark for 16 h. The polymer wasisolated by filtration and the solid washed with water (1-1.51) to yieldthe hydrogen peroxide adduct (Scheme 7).

Method for Determining Oxidant Loading

A sample of the required polymer was suspended in 50% aqueous hydrogenperoxide for 18 h. The polymer was filtered and washed with water,collected and treated with solution of 10% aqueous potassium iodide (0.1M) in acetic acid After standing for 5 minutes a 1% aqueous starchsolution was added and the suspension left to stand for 1 h. Theresulting dark blue coloured solution was titrated with sodiumthiosulfate until the colourless endpoint. The mixture was left for anhour and any further blue coloration of the solution was furthertitrated with sodium thiosulfate until no further colour persisted(Table 9).

TABLE 9 Hydrogen peroxide loading on functionalised polymers. Loading ofLoading of oxidant/ oxidant/ Sample mol g⁻¹ Sample mol g⁻¹ 9a 7.9 × 10⁻⁴9k 2.7 × 10⁻⁵ XAD-4 N/D Tencel N/D 9b 1.2 × 10⁻⁴ 9l 1.7 × 10⁻⁵ PSXL-SN/D Viscose N/D 9c 2.6 × 10⁻⁴ 9m 2.5 × 10⁻⁵ UHMWPE N/D NK-Cotton N/D 9d8.9 × 10⁻⁵ 9n 4.3 × 10⁻⁶ SMUHMWPE N/D MW-Cotton N/D 9e 2.6 × 10⁻⁵ 9o 3.2× 10⁻⁶ PE-S N/D Cotton wool N/D 9f 1.1 × 10⁻⁵ 9p 4.3 × 10⁻⁴ PP N/D PETN/D 9g 1.2 × 10⁻⁶ 9q 2.4 × 10⁻⁶ PP-S N/D Silica N/D 9h 1.5 × 10⁻⁴ 9r 5.9× 10⁻⁶ N-610 N/D Alumina N/D 9i 6.6 × 10⁻⁵ 9s 2.3 × 10⁻⁴ Hybond-N N/DNomex N/D 9j 5.3 × 10⁻⁵ 10 2.3 × 10⁻⁴ Kevlar N/D UHMWPE N/D N/D = Notdetected.

EXAMPLE 11 Biotesting

Method for Biotesting

An agar plate inoculated with the S. Aureus was punched with 10 mmwells. To these wells was added 20 μl of molten agar. When set thepolymer sample was added to the well so that an even thin layer ofpolymer was produced. The well was then sealed with a further 50 μl ofmolten agar, the plate incubated overnight at 37° C. and the zonesmeasured after this (Table 10).

Bioassay Results S. Aureus.

TABLE 10 Zone of inhibition results against S. Aureus using 10 mm wells.Weight of Sample polymer/g Zone/mm 4a 0.087 N/D 9a 0.090 38 XAD-4 + H₂O₂0.091 N/D 4c 0.089 N/D 9c 0.075 37 UHMWPE + H₂O₂ 0.090 N/D 4f 0.090 N/D9f 0.080 22 PP + H₂O₂ 0.090 N/D 4q 0.091 N/D 9q 0.071 N/D Silica + H₂O₂0.090 N/D N/D = Not detected.

1. A process for producing a substrate having a functionalised surface,which process comprises: (a) contacting the substrate with a carbeneprecursor, which carbene precursor is selected from a compound of thefollowing formula (III):

wherein A is an aryl or heteroaryl ring; p is 1, 2, 3, 4 or 5; R¹ isselected from hydrogen, aryl which is unsubstituted or substituted,heteroaryl which is unsubstituted or substituted, C₁-C₁₀ alkoxy which issubstituted or unsubstituted, C₁-C₁₀ alkylamino which is substituted orunsubstituted, di(C₁-C₁₀)alkylamino which is substituted orunsubstituted, C₁-C₁₀ alkylthio which is substituted or unsubstituted,and C₁-C₁₀ alkyl which is unsubstituted or substituted and which isoptionally interrupted by N(R²), O or S wherein R² is H or C₁-C₆ alkyl;Q is selected from —N(Z₁)(Z₂) and —CH₂—V—(W—R)_(n); Z₁ and Z₂ areindependently selected from aryl which is unsubstituted or substituted,heteroaryl which is unsubstituted or substituted, C₁-C₁₀ alkoxy which issubstituted or unsubstituted, C₁-C₁₀ alkylamino which is substituted orunsubstituted, di(C₁-C₁₀)alkylamino which is substituted orunsubstituted, C₁-C₁₀ alkylthio which is substituted or unsubstituted,and C₁-C₁₀ alkyl which is unsubstituted or substituted and which isoptionally interrupted by N(R²), O or S wherein R² is H or C₁-C₆ alkyl;V is -alk, —O-alk-, -alk-O— or -Oalk-O—, wherein alk is C₁-C₁₀ alkylene;W is a functional group of one of the following formulae (a) to (c):

wherein X is O, S or NH₂ ⁺; and R is selected from H, C₁-C₆ alkyl whichis unsubstituted or substituted, aryl which is unsubstituted orsubstituted and heteroaryl which is unsubstituted or substituted; and nis 1, 2 or 3; and a compound of the following formula (IV):

wherein each of A and B, which are the same or different, is an aryl orheteroaryl ring; each of Q and Q², which are the same or different, is—N(Z₁)(Z₂) or —CH₂—V—(W—R)_(n), wherein Z₁, Z₂, V, W, R and n are asdefined above for formula (III); and each of p and r, which are the sameor different, is 1, 2, 3, 4 or 5; (b) generating a carbene reactiveintermediate from the carbene precursor so that it reacts with thesubstrate to functionalise the surface, thereby yielding an activatedsubstrate; and (c) further functionalising the activated substrateobtained in (b).
 2. A process according to claim 1 wherein step (c)comprises treating the activated substrate obtained in step (b) withhydrogen peroxide, to yield a biocidal substrate.
 3. A process accordingto claim 1 wherein step (c) comprises treating the activated substrateobtained in step (b) with a diazonium salt, thereby forming a diazocoupled coloured substrate.
 4. A process according to claim 3 whereinthe diazonium salt is ArNa⁺, wherein Ar is selected from aryl which isunsubstituted or substituted and heteroaryl which is unsubstituted orsubstituted.
 5. A process according to claim 1 wherein step (c)comprises treating the activated substrate obtained in step (b) with afunctionalised diazonium salt, thereby forming a diazo coupled substratewherein the functionality of the diazonium salt confers a desiredactivity on the diazo coupled substrate.
 6. A process according to claim3, which process further comprises: treating the diazo coupled substrateobtained in step (c) with hydrogen peroxide, to yield a biocidal diazocoupled substrate.
 7. A process according to claim 1, wherein thesubstrate comprises a polymer.
 8. A process according to claim 1,wherein the substrate comprises an inorganic material.
 9. A processaccording to claim 1, wherein the substrate comprises a mixture of apolymer and an inorganic filler.
 10. A process according to claim 7,wherein the polymer is a homopolymer or a copolymer.
 11. A processaccording to claim 7, wherein the polymer is selected from polyolefins,polyesters, polyamides, polystyrenics, polytetrafluoroethylene,polyglycosides, polypeptides, polyacrylates, polyacrylics,polycarbonates, polyethers, polyketones, rubbers, polysulfones,polyurethanes, polyvinyls, cellulose and block copolymers.
 12. A processaccording to claim 8, wherein the inorganic material is selected fromsilica, alumina, titania, glass and an allotrope of carbon.
 13. Aprocess according to claim 1, wherein the carbene precursor is selectedfrom bis-4,4′-N,N-dimethylammo diphenyldiazomethane and1-{2-[4-(diazo-phenyl-methyl)-benzyloxy]-ethyl}-3-phenyl urea.
 14. Asubstrate which is obtainable by a process as defined in claim
 1. 15. Abiocidal polymeric substrate which is obtainable by a process as definedin claim
 2. 16. A water purification system, a water filtration system,an air purification system, an item of clothing, an item of surgicalequipment or a medical device which incorporates a biocidal polymericsubstrate as defined in claim
 15. 17. A coloured substrate which isobtainable by a process as defined in claim
 3. 18. An item of packaging,a lens or a security tag which incorporates a coloured substrate asdefined in claim
 17. 19. A compound of formula (I):

wherein each of A and B, which are the same or different, is an aryl orheteroaryl ring; n is an integer of 1 to 3; y is 0 or an integer of 1 to5; z is 0 or an integer of 1 to 5; provided that z and y are not both 0;V is -alk, —O-alk-, -alk-O— or —O-alk-O—, wherein alk is C₁-C₁₀alkylene; W is a functional group of one of the following formulae (a)to (c):

wherein X is O, S or NH₂ ⁺; and R is selected from H, C₁-C₆ alkyl whichis unsubstituted or substituted, aryl which is unsubstituted orsubstituted, and heteroaryl which is unsubstituted or substituted;provided that the compound is not4,4′-bis(N-acetyl-2-aminoethyl)diphenyldiazomethane.
 20. A compoundaccording to claim 19 which is of the following formula (Ia):

wherein y is an integer of 1 to 5 and each of V, W and R is as definedin claim
 19. 21. A compound according to claim 19 wherein y is
 1. 22. Acompound according to claim 19 which is of the following formula (Ib):

wherein each of V, W and R is as defined in claim
 19. 23. A process forproducing a compound of formula (VII) or (VIII):

wherein A is an aryl or heteroaryl ring; B is an aryl or heteroarylring; p is 1, 2, 3, 4 or 5; r is 1, 2, 3, 4 or 5; R¹ is selected fromhydrogen, aryl which is unsubstituted or substituted, heteroaryl whichis unsubstituted or substituted, C₁-C₁₀ alkoxy which is substituted orunsubstituted, C₁-C₁₀ alkylamino which is substituted or unsubstituted,di(C₁-C₁₀)alkylamino which is substituted or unsubstituted, C₁-C₁₀alkylthio which is substituted or unsubstituted, and C₁-C₁₀ alkyl whichis unsubstituted or substituted and which is optionally interrupted byN(R²), O or S wherein R² is H or C₁-C₆ alkyl; Q², which may be the sameas or different from Q, is —N(Z₁)(Z₂); and Z₁ and Z₂ are independentlyselected from aryl which is unsubstituted or substituted, heteroarylwhich is unsubstituted or substituted, C₁-C₁₀ alkoxy which issubstituted or unsubstituted, C₁-C₁₀ alkylamino which is substituted orunsubstituted, di(C₁-C₁₀)alkylamino which is substituted orunsubstituted, C₁C₁₀ alkylthio which is substituted or unsubstituted,and C₁-C₁₀ alkyl which is unsubstituted or substituted and which isoptionally interrupted by N(R), O or S wherein R is H or C₁-C₆ alkyl;the process comprising treating a compound of formula (V) or (VI) withhydrazine in the presence of heat and a solvent:

wherein A, B, Q, Q², p, r and R¹ are as defined above.
 24. A processaccording to claim 23, which process further comprises oxidising acompound of formula (VII) or (VIII) to produce a carbene precursorcompound of formula (III) or (IV) respectively:

wherein A, B, Q, Q², p, r and R¹ are as defined in claim 23.